Versatile roles of extracellular vesicles in cancer

Kosaka, Nobuyoshi; Yoshioka, Yusuke; Fujita, Yu; Ochiya, Takahiro

doi:10.1172/jci81130

Cited by 273 publications

(254 citation statements)

References 104 publications

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“…In general, EVs, including exosomes and microvesicles, are small membrane vesicles that contain various bioactive molecules, such as microRNAs (miRNAs), messenger RNAs and proteins1314151617; they are released from all cell types and play key physiological roles in intercellular communication181920. Ovarian cancer cells aggressively migrate into the peritoneal cavity and the ascetic fluid provides a favourable environment for wide dissemination21.…”

mentioning

confidence: 99%

Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer

Yokoi¹,

Yoshioka²,

Yamamoto³

et al. 2017

Nat Commun

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254

223

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Advanced ovarian cancers are highly metastatic due to frequent peritoneal dissemination, resulting in dismal prognosis. Here we report the functions of cancer-derived extracellular vesicles (EVs), which are emerging as important mediators of tumour metastasis. The EVs from highly metastatic cells strongly induce metastatic behaviour in moderately metastatic tumours. Notably, the cancer EVs efficiently induce apoptotic cell death in human mesothelial cells in vitro and in vivo, thus resulting in the destruction of the peritoneal mesothelium barrier. Whole transcriptome analysis shows that MMP1 is significantly elevated in mesothelial cells treated with highly metastatic cancer EVs and intact MMP1 mRNAs are selectively packaged in the EVs. Importantly, MMP1 expression in ovarian cancer is tightly correlated with a poor prognosis. Moreover, MMP1 mRNA-carrying EVs exist in the ascites of cancer patients and these EVs also induce apoptosis in mesothelial cells. Our findings elucidate a previously unknown mechanism of peritoneal dissemination via EVs.

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mentioning

confidence: 99%

Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer

Yokoi¹,

Yoshioka²,

Yamamoto³

et al. 2017

Nat Commun

Self Cite

254

223

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“…Plasma and serum carry EVs which are small lipid membrane-bound satchels expelled by cells to mediate cellto-cell communication and containing soluble materials such as nucleic acids, lipids and proteins, protected from degradation (15). Emerging evidence suggests that exosomes, small EVs (40-150 nm) with a multivesicular endosomal origin secreted by both normal and neoplastic cells, play a crucial role in facilitating tumorigenesis (16).…”

Section: Mirnas Packaged In Extracellular Vesicles (Evs)mentioning

confidence: 99%

Circulating microRNAs as emerging non-invasive biomarkers for gliomas

Santangelo¹,

Tamanini²,

Cabrini³

et al. 2017

Ann. Transl. Med.

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No single circulating biomarker has been put to practice for malignant gliomas so far, the most lethal primary brain tumors. Many promising protein biomarkers such as the mutant EGFRvIII or glial fibrillary acidic protein (GFAP) have already been detected in the blood and cerebrospinal fluid (CSF) of patients with gliomas, but their clinical value is still pending validation. Furthermore, these and other proteins seem to lack sufficient sensitivity and specificity required for a successful biomarker in this clinical setting. The expression profiling of microRNAs (miRNAs) has already entered cancer clinics as diagnostic and prognostic biomarkers, for assessing tumor initiation, progression and response to treatment. Largescale miRNA expression analyses reported both up-regulation and down-regulation of several miRNAs in tumour tissues from patients with gliomas compared to normal brain tissue, thus supporting the development of miRNA-based biomarkers. Using comprehensive high-throughput approaches, such as microarrays, different circulating miRNAs were proposed as potential biomarkers of gliomas. This review is aimed to summarize the clinical evidence about circulating miRNA biomarkers discovered to date. Mandatory issues to develop clinically validated biomarkers to improve time of diagnosis, predicting response to treatment and prognosis of patients with gliomas are also herein addresses.

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“…First, EVs reflect the physiological state and microenvironment of their cells of origin, and most cells secrete EVs containing specific proteins and nucleic acids [22,23,102]; Second, EVs are found in the blood and other body fluids; Third, EVs are very stable in the extracellular environment after their release from cells because of the phospholipid bilayer. In fact, numerous EV proteins and miRNAs have already been identified as potentially useful biomarkers for various diseases, especially in cancer detection [21,103,104,105]. …”

Section: Circulating Evs and Mirnas As Potential Biomarkers For Copdmentioning

confidence: 99%

“…In general, there are two therapeutic strategies targeting EVs: (1) Eliminating the EVs that contain nucleic acids or proteins as mediators of intracellular communication involved in disease pathogenesis; and (2) Using EVs as a source of lung regenerating or immune modulating agents. Eliminating EVs could be achieved by several different therapeutic approaches, including capturing the circulating EVs, disrupting EVs uptake by recipient cells, and inhibiting EVs production or secretion [103,116]. However, considering the latter strategy, the best examples are treatment with mesenchymal stem/stromal cells (MSCs) derived-EVs [17].…”

Section: Evs As Potential Therapeutics For Copdmentioning

confidence: 99%

Extracellular Vesicles in Chronic Obstructive Pulmonary Disease

Kadota¹,

Fujita

Yoshioka³

et al. 2016

IJMS

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Chronic obstructive pulmonary disease (COPD) is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide. Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell–cell communication tools. They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases. Recently, EVs have attracted considerable attention in pulmonary research. In this review, we summarize the recent findings of EV-mediated COPD pathogenesis. We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD.

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Versatile roles of extracellular vesicles in cancer

Cited by 273 publications

References 104 publications

Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer

Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer

Circulating microRNAs as emerging non-invasive biomarkers for gliomas

Extracellular Vesicles in Chronic Obstructive Pulmonary Disease

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